1. Field of the Invention
The present invention relates to the efficient commercial synthesis for the making of bivalirudin, a peptide. It is well known that bivalirudin is indicated to reduce the risk of acute ischemic complications, and is an anticoagulant and acts as a direct thrombin inhibitor. The process substantially comprises the syntheses of various fragments of the polypeptide and the coupling of the fragments to produce bivalirudin.
2. Description of the Related Arts
Thrombin inhibitors are synthesized by various techniques which are well known in the art. These include enzymatic cleavage of natural or recombinant hirudin, recombinant DNA techniques, solid-phase peptide synthesis, solution-phase peptide synthesis, organic chemical synthesis techniques, or a combination of these techniques.
The following references disclose various techniques for producing thrombin inhibitors.    (1) U.S. Pat. No. 5,196,404    (2) U.S. Pat. No. 5,240,913    (3) U.S. Pat. No. 5,425,936    (4) U.S. Pat. No. 5,433,940    (5) U.S. Pat. No. 5,514,409    (6) U.S. Pat. No. 5,691,311    (7) US 2007093423    (8) US 2008051558    (9) US 2008287648    (10) US 2008287650    (11) US 20090062511    (12) WO9850563
The disclosure of the above references are herein incorporated in their entirety by reference. Certain of the references disclose the solid-phase peptide synthesis for making Bivalirudin, as the synthesis can be rapidly conducted. However, this synthesis method results in low yield and high cost of manufacture.